Transcript Document

Public Health Genomics:
What is it and Why do we Need to Know?
Muin J. Khoury, MD, Ph.D.
CDC Office of Genomics and Disease Prevention
Outline

Overview of Genomics & Emergence of
“Public Health Genomics”

Current US Initiatives in Public Health
Genomics

Action Steps for the Future of Genomics in
Public Health
“Genomics is to the 21st century what
infectious disease was to the 20th
century…”
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“…Genomics should be considered in every facet of public health:
infectious disease, chronic disease, occupational health,
environmental health, in addition to maternal and child health.”
Gerard S, Hayes M, Rothstein MA. J Law Med Ethics. 2002
Who Will Keep the Public Healthy?
(IOM, 2002)
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Critical areas for public health
education in the 21st century
Informatics
Genomics
Communication
Cultural competence
Community-based research
Global health
Policy and law
Public health ethics
Institute of Medicine, 2002
90% US public health schools teach policy but only 15% genomics
How Will Genetics Change Our Lives
50 Years from Now?
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“We will have individualized, preventive medical
care based on our own predicted risk of disease
as assessed by looking at our DNA. By then
each of us will have had our genomes
sequenced because it will cost less than $100 to
do that. And this information will be part of our
medical record. Because we will still get sick,
we'll still need drugs, but these will be tailored to
our individual needs.
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F. Collins MD, PhD, TIME, the Future of Life, 2003
Predicted Home Computers for 2004 !?!
Popular Mechanics Magazine (1954)
Who needs genomics research when it is obvious
what we need to do to prevent common chronic
diseases?
Exercise more
Eat a healthier diet
Stop smoking
Drink alcohol in moderation
Take an aspirin per day
See your doctor
Get screened
Etc.
Health Status of the USA
•
31% of adults are obese
•
Since 1980, obesity rates have doubled among
children and tripled among adolescents
18
16
14
12
10
8
6
4
2
0
Percentage of Overweight U.S. Children
Ages 12-19
Ages 6-11
‘63-70
‘71-74
‘76-80
‘88-94
Source: National Center for Health Statistics
‘99-02
Health Status of the USA
*
From Genetics to Genomics
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Genetic Disorders
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Genetic Information
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Mendelian Disorders
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All Diseases
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Disease burden: 5%
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Disease Burden: 95%
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Mutations/One Gene
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Variants/MultiGenes
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High Disease Risk
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Low Disease Risk
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Environment +/-
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Environment ++
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“Genetic Services”
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General Practice
Mendelian Disorders Featuring CAD/MI
Apolipoprotein(a) excess
Apolipoprotein AI deficiency
Autosomal recessive
hypercholesterolemia
Cerebrotendinous
xanthomatosis
Fabry disease
Familial combined
hyperlipidemia
Familial defective apoB
Familial
hypercholesterolemia
Familial partial lipodystrophy
Familial pseudo hyper
kalemia due to RBCl leak
Heparin cofactor II deficiency
Homocystinuria/homocysteinemi
a
Niemann-Pick disease, type E
Progeria
Protein C deficiency
Pseudoxanthoma elasticum
Sitosterolemia
Spontaneous coronary dissection
Tangier disease
Type III hyperlipoproteinemia
Werner syndrome
Williams syndrome
Human Diseases Result from
Gene-Environment Interaction
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“Some vegetarians with
'acceptable' cholesterol
levels suffer myocardial
infarction in the 30's.
Other individuals...seem
to live forever despite
personal stress,
smoking, obesity, and
poor adherence to a
Heart Associationapproved diet"
R.A. Hegele (1992)
Genetics and Cardiovascular Disease
Stress
Nutrition
Homocysteine
Blood
Pressure
Diabetes
LDL
Cholesterol
Smoking
Health
Status
GENES
Obesity
Fibrinogen
Exercise
Triglycerides
Lp(a)
Insulin
Malaria’s
Battle of Genomes
Environment
Host
Pathogen
What is the Public Health Approach to Genomics?

Using genetic information to improve
health and prevent disease across the
lifespan
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Focus of Public Health
Population health
 Disease prevention and health promotion
 Evidence-based integration into practice
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What is “Public Health Genomics”?
(IOM, 2005)
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“An emerging field
that assesses the
impact of genes and
their interaction with
behavior, diet and the
environment on the
population’s health”
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Use this information to
develop strategies to
prevent disease
Outline

Overview of Genomics & Emergence of
“Public Health Genomics”

Current US Initiatives in Public Health
Genomics

Action Steps for the Future of Genomics in
Public Health
Public Health Approach to Translating Genome
Discoveries into Population Health Benefits
Role of genomic information in
population health?
(35,000 genes)
Value of genomic information
in treatment and prevention?
(1000+ tests)
Implementation of
genomics in practice?
“Systematic application of epidemiologic
methods and approaches to assess the
impact of human genetic variation on
health and disease”
Khoury, Little and Burke, HuGE 2004
• Genotype prevalence
• Gene - disease association
• Gene - gene interactions
• Gene - environment interactions
HuGE problem:
25,000 genes, their
combinations and
interactions with risk
factors
Centers for Birth Defects
Research and Prevention
Iowa
Arkansas
North Carolina
Massachusetts
Multi-state
Population-Based Case-Control
Study
California
Texas
New Birth
JerseyDefects Registries
Based
on
State-Based
Georgia
Utah
New York
1998 Springfield Ironhorse Triathlon
Leptospirosis Outbreak
•
876 triathletes; 12% reported illness
•
Serum from 474; 52 positive for leptospirosis
Genetic studies: TNF-a, HLA-DRB, HLA-DQB
•
DNA from 85 anonymized blood samples
•
HLA-DQ6 positive triathletes (compared to DQ6 negatives)
were
- more likely be seropositive for leptospirosis
(OR=2.8, p=0.04)
- especially for those who reported swallowing lake water
(OR=8.5, p=0.001)
Lingappa J. et al., Genes & Immunity 2004
Khoury MJ, Nat Genet 2004;36:1027-8
Public Health Approach to Translating Genome
Discoveries into Population Health Benefits
Role of genomic information in
population health?
(35,000 genes)
Value of genomic information
in treatment and prevention?
(1000+ tests)
Implementation of
genomics in practice?
AmpliChip CYP450 Microarray Test
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CYP2D6 and CYP2C19
genes
Chip = microarray
detection system to
identify common
mutations (33 variants)
Variations affect how
common drugs are
processed or metabolized

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Analgesics, antidepressants,
antihistamines, heart & blood
pressure drugs
Poor metabolizers  adverse
reactions
Ultrarapid metabolizers 
non-responders
In Store Sales of Genomic Profiles
Evaluation of Genomic Applications in
Practice and Prevention
The ACCE Framework

Disorder/Setting:
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Analytic Validity
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How well does the test correlate with clinical outcomes?
Clinical Utility

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How good is the lab performance?
Clinical Validity
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
Intended Use of Test
Does it make a difference in outcomes?
ELSI
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Ethical, legal and social issues
Evaluating Genomic Applications in
Practice and Prevention (EGAPP)
_________________________________________________
Impact
• Form independent panel to evaluate
genetic tests and other genomic
applications
• Protect public from harm and provide
practitioners with evidence base
• Public Health accepts key leadership
role recommended by many groups
Example: Hereditary Hemochromatosis

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Iron Overload
Multiple organ system
Intervention: simple
Gene Chromosome 6
1997 Expert Panel on
Population Screening
Public health research
Agenda
NHLBI study
CDC Provider education
campaign
Prevalence of
Hereditary Hemochromatosis
Mutations in the USA
NHANES III
Genotype Prevalence (%)
Genotype/Group
White
Black
C282Y/C282Y
H63D/H63D
C282Y/H63D
0.3
2.2
2.4
Hisp
.06
0.3
.06
Steinberg KK et al., JAMA 2001;285:2216
.03
1.1
0.2
Hemochromatosis-Associated Hospitalizations,
National Hospital Discharge Survey 1979-1997
Rate per 100,000 US residents
5
4
3
2
1
males
females
0
79 - 82
83 - 87
88 - 92
Years
Brown al et al. Genet Med 2001;3:109-111
93 – 97
Body Iron Content in grams
Natural History of Hereditary Hemochromatosis
30
Early death
25
Bronze diabetes
20
Signs of organ damage
15
Non-specific symptoms
10
Asymptomatic
5
Mutation
0
0
10
20
30
Age
40
50
60
Public Health Approach to Translating Genome
Discoveries into Population Health Benefits
Role of genomic information in
population health?
(35,000 genes)
Value of genomic information
in treatment and prevention?
(1000+ tests)
Implementation of
genomics in practice?

“The challenge to public health genomics
is to overcome inequitable allocation of
benefits, the tragedy that would befall us if
we made the promise of genetics only for
those who could afford it and not for all
society”

Bill Foege; IOM, 2005
Centers for Excellence in Genomics
and Public Health
_______________________________________________________________
Impact
• 3 Centers provide bridge between
genomics research and practice
• Provide public sector access to
specialized expertise
• Create networked partnership
spanning academic and public
sectors and multiple levels of
government
Integrating Genomics into State
Public Health Programs
_________________________________________________
Impact
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4 states developing
workforce and genomic
applications for public
health practice
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State-to-state networks
to share experience and
expertise
Family History Public Health Initiative
Impact
• Family HealthwareTM
• Validating family history tool
for use by practitioners and the public
for six common diseases
• Goal to improve targeting of screening
and interventions for health impact
What is family history?
Behaviors
Environmental
Exposures
Genetics
Family history is a risk factor for
many chronic diseases
Relative Risk
Heart disease
Breast cancer
Colorectal cancer
Prostate cancer
Melanoma
Type II diabetes
Osteoporosis
Asthma
2.0 – 5.4
2.1 – 3.9
1.7 – 4.9
3.2 – 11.0
2.7 – 4.3
2.4 – 4.0
2.0 – 2.4
3.0 – 7.0
Family History of Common Diseases is
Common in the Population
57%
No family history
33%
One disorder
2%
Three or more disorders
8%
Two disorders
Scheuner et al. Am J Med Genet 1997;71:315-324.
Family history is underutilized in
preventive medicine
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Family history collected at about 50% of new visits
Average duration of visit, 10 minutes; average
duration of family history discussion, 2.5 minutes
Acheson et al., 2000
Only 29% of PCPs feel prepared to take family
history and draw pedigrees
Suchard et al., 1999
Family history Risk Stratification Concept
Assessment
Risk stratification
Average
Family
History
Tool
Intervention
Standard prevention
recommendations
Moderate
Personalized prevention
recommendations
High
personalized prevention
recommendations & referral
for genetic evaluation
Use of Family History Can Help Achieve
Population Health Goals
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14% of families account for almost half of
the burden of heart attacks in Utah (Hunt 2003)
Almost half the population has a family history of a
close relative with one or more common chronic diseases
(Scheuner, 1997)
More than 70% of adults with diabetes have a family
history of diabetes (Hariri et al, 2005)
Public Health Utility of Family History

“Family History effectively bridges clinical
medicine with public health by focusing
risk assessment at a level between the
extremes of “one at a time” and “one size
fits all”

Hunt S, et al. Am J Prev Med 2003;24:136.
Outline

Overview of Genomics & Emergence of
“Public Health Genomics”

Current US Initiatives in Public Health
Genomics

Action Steps for the Future of Genomics in
Public Health
What Should Public Health do Now?

Action Steps
Account for both modifiable and non-modifiable
risk factors in designing public health
interventions

Support the development and enactment of
policies related to ethical and effective use of
genome-based knowledge for population
health

Develop partnerships with stakeholders
What should Public Health do Now?
 Educate
ourselves and our constituents
 Use
existing population data sources to
help determine genetic contributions to
disease and gene-environment interaction
 Identify
populations at high and moderate
risk who could benefit the most from
medical, behavioral and environmental
interventions
Summary Points

Genomics will affect public health practice
beyond the traditional domain of genetic
diseases

Scientific gaps exist in translating gene
discoveries into population health benefits

We are seeing the emergence of “public health
genomics” as a multidisciplinary field for the
21st Century
Summary Points:
Current Applications of “Public Health
Genomics”

Why do populations and communities get sick?

How can we use genetic tests for population
health?
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How can we use family medical history?

How can we prepare the workforce and the
general public?

How can we influence public policy and health
services for effective and ethical integration of
new science into practice?
We have already taken the first steps on
the translation highway from gene
discovery to population health !
http://www.cdc.gov/genomics/activities/ogdp/2003.htm